TNNI1 (Troponin I, slow skeletal muscle) variants and mutations
TNNI1 (also known as Troponin I, slow skeletal muscle) is a human protein-coding gene encoding a troponin I, slow skeletal muscle protein. It provides the inhibitory troponin subunit in slow skeletal muscle, restraining actin-myosin interaction when calcium is low. Pathogenic human disease associations are limited compared with cardiac troponin genes, but altered function can affect skeletal-muscle contractile regulation. This analysis covers 367 TNNI1 variants and mutations. Of these, 77% have computational variant effect predictions. Disease context includes neurodegenerative disease, diaphragm disorder, and Blount disease. Example TNNI1 variants include P2L, V4I, and E5D.
Variant analysis overview
- Gene: TNNI1
- Protein: Troponin I, slow skeletal muscle
- UniProt accession: P19237
- Organism: Homo sapiens
- Variants analyzed: 367
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 205 unspecified-consequence records; 71 synonymous variants; 76 missense variants; 2 stop-gained variants; 6 frameshift variants; 5 splice-region variants; 2 in-frame deletions; 1 in-frame insertions; 2 substitution
- Prediction scores: 283 variants have prediction scores (77% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurodegenerative disease, diaphragm disorder, Blount disease, tibial hemimelia, tibia, hypoplasia or aplasia of, with polydactyly, Absent tibia - polydactyly, hallux varus-preaxial polysyndactyly syndrome, Hallux varus - preaxial polysyndactyly, Syndactyly type 2, metaphyseal anadysplasia, syndactyly type 1, pacman dysplasia.
Protein structure and variant hotspots
- Protein features: 2 post-translational modification sites.
- PTM context: 6 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable TNNI1 variants
Examples include P2L, V4I, E5D, E5K, E5V, R6G, K7E, P8H. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- P2L (p.Pro2Leu), cosmic curated COSV10966, ExAC rs770804434, TOPMed rs770804434, gnomAD rs770804434, REVEL 0.54, CADD 28.50, Uncertain significance, not specified
- V4I (p.Val4Ile), Ensembl rs1571738756
- E5D (p.Glu5Asp), Ensembl rs2102373087
- E5K (p.Glu5Lys), rs201326771, ClinGen CA1325558, cosmic curated COSV60190, ClinVar RCV004082974, REVEL 0.50, CADD 23.00, Uncertain significance, not specified
- E5V (p.Glu5Val), TOPMed rs1662756424
- R6G (p.Arg6Gly), cosmic curated COSV60188
- K7E (p.Lys7Glu), TOPMed rs1662713214, gnomAD rs1662713214, REVEL 0.81, CADD 27.20
- P8H (p.Pro8His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K9* (p.Lys9Ter), cosmic curated COSV60188
- K9N (p.Lys9Asn), gnomAD rs1364161527, REVEL 0.63, CADD 26.70
- K9R (p.Lys9Arg), TOPMed rs1662713179
- I10M (p.Ile10Met), gnomAD rs1162259668, REVEL 0.54, CADD 22.10
- I10V (p.Ile10Val), TOPMed rs1662713094
- A12T (p.Ala12Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R14C (p.Arg14Cys), rs771077280, ClinGen CA1325535, cosmic curated COSV10465, ClinVar RCV003333902, REVEL 0.82, CADD 28.60, Uncertain significance, TNNI1-related disorder; TNNI1-related congenital myopathy
- R14H (p.Arg14His), cosmic curated COSV10027, ExAC rs747286830, TOPMed rs747286830, gnomAD rs747286830, REVEL 0.81, CADD 29.80, Uncertain significance, TNNI1-related disorder
- R14L (p.Arg14Leu), ExAC rs747286830, TOPMed rs747286830, gnomAD rs747286830, REVEL 0.86, CADD 28.90
- R14S (p.Arg14Ser), cosmic curated COSV10027
- K15N (p.Lys15Asn), cosmic curated COSV10648
- L16P (p.Leu16Pro), NCI-TCGA Cosmic COSV6018, cosmic curated COSV60188, Variant assessed as somatic; moderate impact.
- K19N (p.Lys19Asn), NCI-TCGA Cosmic COSV6019, Variant assessed as somatic; moderate impact.
- S20R (p.Ser20Arg), 1000Genomes rs201837726, ExAC rs201837726, TOPMed rs201837726, gnomAD rs201837726, REVEL 0.75, CADD 25.70
- S20S (p.Ser20Ser), rs201837726, gnomAD 1-201414647-G-A, CADD 16.70
- S20I (p.Ser20Ile), gnomAD 1-201414648-C-A, REVEL 0.77, CADD 28.40
- L21P (p.Leu21Pro), TOPMed rs1294933494, gnomAD rs1294933494, REVEL 0.96, CADD 32.00
- M22T (p.Met22Thr), Ensembl rs1571736869
- L23M (p.Leu23Met), cosmic curated COSV10519
- L23L (p.Leu23Leu), gnomAD 1-201414638-C-T, CADD 13.20
- A24T (p.Ala24Thr), NCI-TCGA TCGA novel, REVEL 0.49, CADD 25.20, Variant assessed as somatic; moderate impact.
- A24V (p.Ala24Val), NCI-TCGA Cosmic COSV6018, cosmic curated COSV60189, Variant assessed as somatic; moderate impact.
- K25N (p.Lys25Asn), gnomAD 1-201414632-C-G, REVEL 0.57, CADD 24.30
- A26T (p.Ala26Thr), cosmic curated COSV10886
- A26V (p.Ala26Val), gnomAD 1-201414630-G-A, REVEL 0.95, CADD 32.00
- K27R (p.Lys27Arg), ExAC rs745403328, TOPMed rs745403328, gnomAD rs745403328, REVEL 0.62, CADD 26.20
- E28A (p.Glu28Ala), cosmic curated COSV60189
- E28G (p.Glu28Gly), TOPMed rs1662702800, REVEL 0.72, CADD 26.90
- E28K (p.Glu28Lys), TOPMed rs1454856567, gnomAD rs1454856567, REVEL 0.74, CADD 25.10
- E28E (p.Glu28Glu), rs1553294614, gnomAD 1-201414623-T-C, CADD 11.50
- C29G (p.Cys29Gly), TOPMed rs1201146437
- W30* (p.Trp30Ter), cosmic curated COSV10465, Ensembl rs868626401, CADD 39.00
- E31K (p.Glu31Lys), cosmic curated COSV10519
- E33* (p.Glu33Ter), 1000Genomes rs373597502, ESP rs373597502, ExAC rs373597502, TOPMed rs373597502, CADD 39.00
- E33G (p.Glu33Gly), gnomAD rs1321908492
- E33K (p.Glu33Lys), 1000Genomes rs373597502, ESP rs373597502, ExAC rs373597502, TOPMed rs373597502, REVEL 0.92, CADD 24.70
- H34Q (p.His34Gln), gnomAD 1-201414605-G-C, REVEL 0.24, CADD 0.12
- H34H (p.His34His), rs144272553, gnomAD 1-201414605-G-A, CADD 0.80
- E35K (p.Glu35Lys), rs199605300, cosmic curated COSV60188, ESP rs199605300, ExAC rs199605300, REVEL 0.20, CADD 17.50, Variant assessed as somatic; moderate impact.
- E35E (p.Glu35Glu), gnomAD 1-201414602-C-T, CADD 9.68
- E35Q (p.Glu35Gln), gnomAD 1-201414604-C-G, REVEL 0.17, CADD 16.20
- E36K (p.Glu36Lys), gnomAD rs1173154951, REVEL 0.36, CADD 22.60
- E36del (p.Glu36del), rs897039592, gnomAD 1-201414598-GCTC-, CADD 18.90
- E36E (p.Glu36Glu), rs1662702292, gnomAD 1-201414599-C-T, CADD 8.16
- E36V (p.Glu36Val), gnomAD 1-201414600-T-A, REVEL 0.28, CADD 22.40
- R37C (p.Arg37Cys), ExAC rs763864468, TOPMed rs763864468, gnomAD rs763864468, REVEL 0.61, CADD 28.80
- R37H (p.Arg37His), rs150769331, ESP rs150769331, ExAC rs150769331, TOPMed rs150769331, REVEL 0.32, CADD 23.20, Uncertain significance, not specified
- R37S (p.Arg37Ser), ExAC rs763864468, TOPMed rs763864468, gnomAD rs763864468, REVEL 0.34, CADD 23.90
- R37R (p.Arg37Arg), rs752668435, gnomAD 1-201414596-G-A, CADD 1.06
- E38G (p.Glu38Gly), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10027, Variant assessed as somatic; moderate impact.
- E38K (p.Glu38Lys), cosmic curated COSV10465, ExAC rs765186576, gnomAD rs765186576, REVEL 0.49, CADD 22.40
- E38E (p.Glu38Glu), rs1040207758, gnomAD 1-201414593-C-T, CADD 11.50
- E40G (p.Glu40Gly), cosmic curated COSV60190
- E40E (p.Glu40Glu), gnomAD 1-201414587-C-T, CADD 13.60
- E40Q (p.Glu40Gln), gnomAD 1-201414589-C-G, REVEL 0.47, CADD 23.50
- K41K (p.Lys41Lys), rs1248906378, gnomAD 1-201414584-C-T, CADD 11.50
- R43C (p.Arg43Cys), rs201145849, NCI-TCGA Cosmic COSV6019, cosmic curated COSV60190, 1000Genomes rs201145849, REVEL 0.72, CADD 29.50, Uncertain significance, not specified
- R43H (p.Arg43His), rs182471625, NCI-TCGA Cosmic COSV6018, cosmic curated COSV60188, 1000Genomes rs182471625, REVEL 0.60, CADD 24.30, Variant assessed as somatic; moderate impact.
- R43P (p.Arg43Pro), 1000Genomes rs182471625, ExAC rs182471625, TOPMed rs182471625, gnomAD rs182471625, REVEL 0.71, CADD 24.60
- R43S (p.Arg43Ser), 1000Genomes rs201145849, ExAC rs201145849, TOPMed rs201145849, gnomAD rs201145849, REVEL 0.50, CADD 23.70
- Y44Y (p.Tyr44Tyr), gnomAD 1-201414575-G-A, CADD 10.40
- Y44F (p.Tyr44Phe), gnomAD 1-201414576-T-A, REVEL 0.80, CADD 24.80
- L45V (p.Leu45Val), gnomAD 1-201414574-G-C, REVEL 0.88, CADD 23.80
- L45L (p.Leu45Leu), rs116486165, gnomAD 1-201414574-G-A, CADD 12.70
- A46T (p.Ala46Thr), cosmic curated COSV60190, gnomAD rs1043296628, REVEL 0.30, CADD 20.20
- A46V (p.Ala46Val), gnomAD 1-201414570-G-A, REVEL 0.40, CADD 24.30
- E47D (p.Glu47Asp), TOPMed rs1331826228
- E47K (p.Glu47Lys), ExAC rs774762591, TOPMed rs774762591, gnomAD rs774762591, REVEL 0.80, CADD 27.70
- R48C (p.Arg48Cys), rs142145258, ClinGen CA1325494, ClinVar RCV004113623, 1000Genomes rs142145258, REVEL 0.79, CADD 31.00, Uncertain significance, not specified
- R48G (p.Arg48Gly), 1000Genomes rs142145258, ESP rs142145258, ExAC rs142145258, TOPMed rs142145258, REVEL 0.77, CADD 24.80, Uncertain significance
- R48H (p.Arg48His), rs200415229, ClinGen CA1325493, ClinVar RCV004230580, 1000Genomes rs200415229, REVEL 0.53, CADD 23.70, Uncertain significance, not specified
- R48R (p.Arg48Arg), gnomAD 1-201414563-G-A, CADD 14.20
- R48S (p.Arg48Ser), gnomAD 1-201414565-G-T, REVEL 0.74, CADD 23.00
- I49L (p.Ile49Leu), TOPMed rs1488949215, gnomAD rs1488949215, REVEL 0.24, CADD 21.70
- I49M (p.Ile49Met), TOPMed rs1211814397
- I49N (p.Ile49Asn), gnomAD rs1365395098, REVEL 0.58, CADD 24.50
- P50H (p.Pro50His), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10027, Variant assessed as somatic; moderate impact.
- P50P (p.Pro50Pro), gnomAD 1-201414557-G-A, CADD 6.75
- T51K (p.Thr51Lys), ESP rs372956100, ExAC rs372956100, TOPMed rs372956100, gnomAD rs372956100, REVEL 0.34, CADD 22.90
- T51M (p.Thr51Met), rs372956100, ESP rs372956100, ExAC rs372956100, TOPMed rs372956100, REVEL 0.35, CADD 23.00, Uncertain significance, not specified
- T51T (p.Thr51Thr), rs144110863, gnomAD 1-201414554-C-T, CADD 6.61
- L52P (p.Leu52Pro), cosmic curated COSV60189
- L52V (p.Leu52Val), ExAC rs756932579, gnomAD rs756932579, REVEL 0.47, CADD 22.20
- L52L (p.Leu52Leu), rs746701305, gnomAD 1-201414551-C-A, CADD 11.20
- Q53* (p.Gln53Ter), Ensembl rs1662700950, CADD 42.00
- Q53K (p.Gln53Lys), gnomAD 1-201414550-G-T, REVEL 0.21, CADD 19.80
- T54P (p.Thr54Pro), Ensembl rs1571736771
- T54T (p.Thr54Thr), gnomAD 1-201414545-G-T, CADD 7.19
- p.Thr54 Arg55insGly, gnomAD 1-201414545-G-GCC, CADD 18.00
- T54A (p.Thr54Ala), gnomAD 1-201414547-T-C, REVEL 0.35, CADD 23.40
- R55C (p.Arg55Cys), 1000Genomes rs545684730, ExAC rs545684730, TOPMed rs545684730, gnomAD rs545684730, REVEL 0.31, CADD 23.30
- R55G (p.Arg55Gly), 1000Genomes rs545684730, ExAC rs545684730, TOPMed rs545684730, gnomAD rs545684730, REVEL 0.23, CADD 19.70, Uncertain significance, not specified
- R55H (p.Arg55His), ExAC rs747617955, TOPMed rs747617955, gnomAD rs747617955, REVEL 0.25, CADD 23.10
- R55S (p.Arg55Ser), 1000Genomes rs545684730, ExAC rs545684730, TOPMed rs545684730, gnomAD rs545684730, REVEL 0.20, CADD 15.20, Uncertain significance, not specified
- R55R (p.Arg55Arg), rs1393405629, gnomAD 1-201414542-A-C, CADD 1.02
- R55L (p.Arg55Leu), gnomAD 1-201414543-C-A, REVEL 0.26, CADD 22.00
- G56D (p.Gly56Asp), Ensembl rs1662700547
- G56S (p.Gly56Ser), ExAC rs778146104, TOPMed rs778146104, gnomAD rs778146104, REVEL 0.46, CADD 22.30
- G56G (p.Gly56Gly), rs750496317, gnomAD 1-201414539-G-A, CADD 8.18
- G56V (p.Gly56Val), gnomAD 1-201414540-C-A, REVEL 0.88, CADD 25.20
- L57M (p.Leu57Met), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10027, REVEL 0.21, CADD 18.40, Variant assessed as somatic; moderate impact.
- L57L (p.Leu57Leu), gnomAD 1-201414536-C-A, CADD 10.40
- L57P (p.Leu57Pro), gnomAD 1-201414537-A-G, REVEL 0.84, CADD 28.70
- S58P (p.Ser58Pro), TOPMed rs1662700446, REVEL 0.83, CADD 25.30
- S58S (p.Ser58Ser), gnomAD 1-201414533-G-A, CADD 7.46
- S58Y (p.Ser58Tyr), gnomAD 1-201414534-G-T, REVEL 0.81, CADD 26.30
- S58F (p.Ser58Phe), gnomAD 1-201414534-G-A, REVEL 0.83, CADD 27.30
- S58T (p.Ser58Thr), gnomAD 1-201414535-A-T, REVEL 0.50, CADD 21.10
- L59F (p.Leu59Phe), gnomAD rs1662700405
- L59L (p.Leu59Leu), gnomAD 1-201414530-G-T, CADD 10.30
- L59H (p.Leu59His), gnomAD 1-201414531-A-T, REVEL 0.67, CADD 24.50
- L59P (p.Leu59Pro), gnomAD 1-201414531-A-G, REVEL 0.82, CADD 25.20
- L59I (p.Leu59Ile), gnomAD 1-201414532-G-T, REVEL 0.25, CADD 21.70
- S60S (p.Ser60Ser), rs1662700316, gnomAD 1-201414527-A-G, CADD 2.95
- S60R (p.Ser60Arg), gnomAD 1-201414527-A-C, REVEL 0.46, CADD 2.00
- S60N (p.Ser60Asn), gnomAD 1-201414528-C-T, REVEL 0.22, CADD 19.60
- S60I (p.Ser60Ile), gnomAD 1-201414528-C-A, REVEL 0.42, CADD 21.80
- S60C (p.Ser60Cys), gnomAD 1-201414529-T-A, REVEL 0.49, CADD 23.40
- S60G (p.Ser60Gly), gnomAD 1-201414529-T-C, REVEL 0.32, CADD 21.50
- A61D (p.Ala61Asp), Ensembl rs1662700276, REVEL 0.20, CADD 21.90
- A61V (p.Ala61Val), cosmic curated COSV60188, REVEL 0.27, CADD 23.30
- A61A (p.Ala61Ala), rs1662700214, gnomAD 1-201414524-G-T, CADD 11.70
- A61T (p.Ala61Thr), gnomAD 1-201414526-C-T, REVEL 0.25, CADD 23.20
- A61S (p.Ala61Ser), gnomAD 1-201414526-C-A, REVEL 0.24, CADD 22.90
- L62R (p.Leu62Arg), gnomAD 1-201414521-CA-C, CADD 32.00
- L62L (p.Leu62Leu), gnomAD 1-201414521-C-A, CADD 10.70
- L62P (p.Leu62Pro), gnomAD 1-201414522-A-G, REVEL 0.99, CADD 29.90
- L62C (p.Leu62Cys), gnomAD 1-201414522-AG-A, CADD 32.00
- L62M (p.Leu62Met), gnomAD 1-201414523-G-T, REVEL 0.86, CADD 25.70
- L62V (p.Leu62Val), gnomAD 1-201414523-G-C, REVEL 0.85, CADD 23.70
- Q63K (p.Gln63Lys), TOPMed rs1390950239, gnomAD rs1390950239, REVEL 0.48, CADD 23.70
- Q63L (p.Gln63Leu), Ensembl rs2102371692, REVEL 0.82, CADD 32.00
- Q63H (p.Gln63His), gnomAD 1-201414518-C-A, REVEL 0.85, CADD 35.00
- Q63Q (p.Gln63Gln), gnomAD 1-201414518-C-T, CADD 26.50
- Q63R (p.Gln63Arg), gnomAD 1-201414519-T-C, REVEL 0.62, CADD 32.00
- Q63* (p.Gln63Ter), gnomAD 1-201414520-G-A, CADD 60.00
- D64H (p.Asp64His), gnomAD rs1435767838, REVEL 0.76, CADD 29.00
- L65V (p.Leu65Val), TOPMed rs1411630180
- L65L (p.Leu65Leu), gnomAD 1-201413116-C-T, CADD 10.20
- C66C (p.Cys66Cys), rs1290152878, gnomAD 1-201413113-G-A, CADD 13.20
- C66W (p.Cys66Trp), gnomAD 1-201413113-G-C, REVEL 0.89, CADD 29.30
- R67G (p.Arg67Gly), 1000Genomes rs2296695, ExAC rs2296695, TOPMed rs2296695, gnomAD rs2296695, REVEL 0.80, CADD 24.50
- R67Q (p.Arg67Gln), cosmic curated COSV60189, gnomAD rs1326534909, REVEL 0.38, CADD 23.00
- R67W (p.Arg67Trp), rs2296695, cosmic curated COSV60188, UniProt VAR 052403, 1000Genomes rs2296695, REVEL 0.79, CADD 29.50, Variant assessed as somatic; moderate impact.
- R67R (p.Arg67Arg), gnomAD 1-201413110-C-T, CADD 11.80
- E68G (p.Glu68Gly), ExAC rs771706605, gnomAD rs771706605, REVEL 0.85, CADD 29.30
- E68K (p.Glu68Lys), cosmic curated COSV10648
- L69M (p.Leu69Met), NCI-TCGA Cosmic COSV6018, Variant assessed as somatic; moderate impact.
- L69L (p.Leu69Leu), gnomAD 1-201413104-C-T, CADD 9.66
- H70D (p.His70Asp), gnomAD rs1662666446, REVEL 0.95, CADD 29.90
- H70Q (p.His70Gln), cosmic curated COSV60188, REVEL 0.67, CADD 7.14, Uncertain significance, not specified
- H70H (p.His70His), rs138552643, gnomAD 1-201413101-G-A, CADD 0.42
- A71T (p.Ala71Thr), 1000Genomes rs12354200, ESP rs12354200, ExAC rs12354200, TOPMed rs12354200, REVEL 0.41, CADD 22.50
- A71V (p.Ala71Val), Ensembl rs2102370821, REVEL 0.56, CADD 22.80
- K72K (p.Lys72Lys), rs1435509884, gnomAD 1-201413095-C-T, CADD 11.60
- K72M (p.Lys72Met), gnomAD 1-201413096-T-A, REVEL 0.80, CADD 28.80
- V73M (p.Val73Met), TOPMed rs1055611269, gnomAD rs1055611269, REVEL 0.79, CADD 25.10, Uncertain significance, not specified
- V73V (p.Val73Val), rs1662666125, gnomAD 1-201413092-C-T, CADD 10.20
- V73G (p.Val73Gly), gnomAD 1-201413093-A-C, REVEL 0.93, CADD 33.00
- E74D (p.Glu74Asp), rs956135288, NCI-TCGA Cosmic COSV6018, cosmic curated COSV60189, TOPMed rs956135288, REVEL 0.25, CADD 16.60, Variant assessed as somatic; moderate impact.
- p.Glu74 Val76del, gnomAD 1-201413080-ATCCA, CADD 20.20
- E74E (p.Glu74Glu), rs956135288, gnomAD 1-201413089-C-T, CADD 11.40
- E74K (p.Glu74Lys), gnomAD 1-201413091-C-T, REVEL 0.59, CADD 23.90
- V75A (p.Val75Ala), cosmic curated COSV60189
- V75V (p.Val75Val), rs1662666029, gnomAD 1-201413086-C-T, CADD 12.60
- V76A (p.Val76Ala), TOPMed rs1662665993, REVEL 0.86, CADD 24.70
- D77E (p.Asp77Glu), TOPMed rs1324527259, gnomAD rs1324527259, REVEL 0.69, CADD 17.80
- D77N (p.Asp77Asn), Ensembl rs867895141
- D77H (p.Asp77His), gnomAD 1-201413082-C-G, REVEL 0.98, CADD 27.40
- E78A (p.Glu78Ala), gnomAD rs1463076821, REVEL 0.96, CADD 26.90
- E79E (p.Glu79Glu), rs140930311, gnomAD 1-201413074-C-T, CADD 7.34
- R80* (p.Arg80Ter), rs1159048123, gnomAD rs1159048123, CADD 36.00, Variant assessed as somatic; high impact.
Public TNNI1 analysis runs
- TNNI1 analysis run — TNNI1 (367 variants) — completed 2026-08-21